scholarly journals Perindoprilat Changes ANG (1-9) Production in Renal Arteries Isolated From Young Spontaneously Hypertensive Rats After ANG I Incubation

2016 ◽  
pp. 561-570
Author(s):  
P. P. WOŁKOW ◽  
B. BUJAK-GIŻYCKA ◽  
J. JAWIEŃ ◽  
R. OLSZANECKI ◽  
J. MADEJ ◽  
...  

We used mass spectrometry to quantitate production of angiotensinogen metabolites in renal artery of 3- and 7-month-old Wistar-Kyoto (WKY) and Spontaneously Hypertensive Rats (SHR). Tissue fragments were incubated for 15 min in oxygenated buffer, with added angiotensin I. Concentrations of angiotensins I (ANG I), II (ANG II), III (ANG III), IV (ANG IV), angiotensin (1-9) [ANG (1-9)], angiotensin (1-7) [ANG (1-7)], and angiotensin (1-5) [ANG (1-5)], excreted into the buffer during experiment, were measured using liquid chromatography-mass spectrometry (LC/MS) and expressed per mg of dry tissue. Effects of pretreatment with 10 μM perindoprilat on the production of ANG I metabolites were quantitated. Background production of any of ANG I metabolites differed neither between WKY and SHR rats nor between 3- and 7-month-old rats. Perindoprilat pretreatment of renal arteries resulted, as expected, in decrease of ANG II production. However, renal arteries of 7-month-old SHR rats were resistant to ACE inhibitor and did not change ANG II production in response to perindoprilat. In renal arteries, taken from 3-month-old rats, pretreated with perindoprilat, incubation with ANG I, resulted in the level of ANG (1-9) significantly higher in SHR than WKY rats. Our conclusion is that in SHR rats, sensitivity of renal artery ACE to perindoprilat inhibition changes with age.

1984 ◽  
Vol 66 (6) ◽  
pp. 717-723 ◽  
Author(s):  
I. Aracon-Birlouez ◽  
T. Montenay-Carestier ◽  
M. A. Devynck

1. Fluorescence Dolarization of dbhenvlhexa-triene embedded in membranes was used as an index of ‘microviscosity’ in platelets and ervthro—cyte ghosts of spontaneously hypertensive rats of the Okamoto-Aoki strain (SHR), Wistar-Kyoto strain (WKY) and of the hypertension-prone and -resistant Sabra strains (SBH and SBN), and the original Sabra strain (SB). 2. Microviscosity was increased both in erythrocyte ghosts and platelet membranes of male but not female SHR rats compared with WKY rats and in hypertension-prone Sabra rats compared with the original Sabra rats. 3. Acute and chronic salt loading increased the microviscosity of platelet membranes in all strains of rats but had no effect on the erythrocyte membranes. 4. Microviscosities of vesicles made of lipids extracted from SHR and WKY erythrocyte ghosts were similar. This supports the hypothesis that membrane proteins play a major role in the differences in microviscosity observed in SHR rats.


2003 ◽  
Vol 89 (4) ◽  
pp. 539-548 ◽  
Author(s):  
Sophie Robin ◽  
Véronique Maupoil ◽  
Frédérique Groubatch ◽  
Pascal Laurant ◽  
Alain Jacqueson ◽  
...  

The objectives of the present work were to evaluate the effect of a methionine-supplemented diet as a model of hyperhomocysteinaemia on the systolic blood pressure (BP) and vasomotor functions of aortic rings in Wistar–Kyoto (WKY) and spontaneously hypertensive rats (SHR). WKY and SHR rats, randomised into four groups, were fed a normal semisynthetic diet or a methionine (8 g/kg)-supplemented diet for 10 weeks. Systolic BP was measured non-invasively. At the end of the experiment, plasma homocysteine, methionine, cysteine and glutathione levels were determined. Vasoconstriction and vasodilatation of aortic rings were measured. The methionine-supplemented diet induced a significant increase in plasma homocysteine and methionine concentration in both WKY and SHR rats, an increase in plasma cysteine concentrations in WKY rats and an increase in the glutathione concentration in SHR. The systolic BP of WKY rats fed the methionine-supplemented diet increased significantly (P<0·01), whereas systolic BP was reduced in SHR. An enhanced aortic responsiveness to noradrenaline and a decreased relaxation induced by acetylcholine and bradykinin were observed in the WKY rats fed the methionine-enriched diet. In SHR, the bradykinin-induced relaxation was reduced, but the sodium nitroprusside response was increased. In conclusion, a methionine-enriched diet induced a moderate hyperhomocysteinaemia and an elevated systolic BP in WKY rats that was consistent with the observed endothelial dysfunction. In SHR, discrepancies between the decreased systolic BP and the vascular alterations suggest more complex interactions of the methionine-enriched diet on the systolic BP. Further investigations are needed to understand the paradoxical effect of a methionine-rich diet on systolic BP.


1994 ◽  
Vol 266 (4) ◽  
pp. F586-F591 ◽  
Author(s):  
T. Okuda ◽  
Y. Inishi ◽  
T. Arakawa ◽  
M. Ohara ◽  
K. Kurokawa

The effects of extracellular Cl- concentration ([Cl-]o) on cultured mesangial cells from spontaneously hypertensive rats (SHR) were examined. Angiotensin II (ANG II)- and vasopressin (VP)-induced cell contraction and Ca2+ transients of SHR mesangial cells were unaffected when the cells were preincubated with 10 mM [Cl-]o, while obvious suppression of the responses to these agents was observed in Wistar-Kyoto (WKY) mesangial cells. Enhanced prostaglandin E2 (PGE2) production was elicited by a decrease in [Cl-]o in WKY mesangial cells. In contrast, PGE2 synthesis by SHR mesangial cells was not enhanced by low [Cl-]o. However, ANG II-stimulated PGE2 production and the attenuation of ANG II-induced cell contraction and Ca2+ transients by the addition of exogenous PGE2 were present equally in both WKY and SHR mesangial cells. Based on these findings, we conclude that the absence of modification of mesangial cell function by [Cl-]o in SHR is due to the inability of low [Cl-]o to enhance PGE2 production. Insensitivity of SHR mesangial cells to changes in [Cl-]o might underlie the dysregulation of renal function in SHR.


2007 ◽  
Vol 292 (1) ◽  
pp. E16-E23 ◽  
Author(s):  
Barbara Peters ◽  
Philipp Teubner ◽  
Susanne Clausmeyer ◽  
Tanja Puschner ◽  
Christiane Maser-Gluth ◽  
...  

ANG II and potassium are known to increase steroidogenic acute regulatory protein (StAR) levels. However, a corresponding increase in StAR mRNA levels has so far been observed only in response to ANG II. We therefore studied the regulation of adrenal StAR mRNA expression in the context of dietary potassium-stimulated aldosterone production. Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were fed a diet containing either 1 or 4% KCl for 5 days. The high-potassium diet increased StAR mRNA levels within the zona glomerulosa in both strains, as demonstrated by in situ hybridization. However, aldosterone production increased in WKY but not in SHR (WKY: from 22.8 ± 4.8 to 137 ± 25 ng/100 ml, P < 0.001, vs. SHR: from 29 ± 3.8 to 51 ± 10.2 ng/100 ml, not significant). This increase was associated with an increase in Cyp11b2 mRNA levels in WKY (3-fold; P < 0.001) but not in SHR. In both strains, the 4% KCl diet was associated with increased plasma renin-independent aldosterone production, as indicated by the marked increase of the aldosterone-to-renin ratios (from 1.4 ± 0.3 to 9 ± 3 in WKY and from 3 ± 1 to 14 ± 5 in SHR; P < 0.002). We conclude that an increase of StAR mRNA levels within the outer cortex is involved in the long-term adrenal response to potassium. This increase alone is not sufficient to increase aldosterone production in the presence of normal Cyp11b2 mRNA levels.


1998 ◽  
Vol 275 (6) ◽  
pp. E1007-E1015 ◽  
Author(s):  
Ji-Ming Ye ◽  
Eric Q. Colquhoun

In the rat muscle vascular bed, vasoconstrictors either increase or decrease oxygen consumption (V˙o 2). The present study compared the effects of norepinephrine (NE), angiotensin II (ANG II), and 5-hydroxytryptamine (5-HT) on vasoconstriction-associated metabolism in the constant-flow perfused hindlimb of spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) in the absence of insulin. Basal perfusion pressure,V˙o 2, glucose uptake, and lactate production were increased by 21.4, 11.9, 46.4, and 44.9% ( P < 0.05 for all), respectively, in SHR, which also had higher blood pressure and metabolic rate ( P < 0.05) in vivo. Dose-response curves for NE-induced perfusion pressure,V˙o 2, and lactate production in SHR were shifted to the left compared with WKY. Associated with the increased perfusion pressure, NE-inducedV˙o 2 and glucose uptake were both decreased ( P < 0.01), particularly at high concentrations. These differences were unaffected by 10 μM propranolol but were all diminished by further addition of prazosin (2.5 nM). ANG II stimulatedV˙o 2, glucose uptake, and lactate production in both strains, but the increased lactate production was smaller in SHR ( P < 0.05) with a proportional decrease ( P< 0.05) in glucose uptake. Conversely, 5-HT decreasedV˙o 2 in both strains ( P < 0.01), and this effect was greater in SHR ( P < 0.01). These data suggest that SHR muscle thermogenesis and glucose uptake are impaired during vasoconstriction, especially in response to NE.


1993 ◽  
Vol 265 (6) ◽  
pp. R1304-R1310 ◽  
Author(s):  
N. Castanon ◽  
E. D. Hendley ◽  
X. M. Fan ◽  
P. Mormede

The behavioral and neuroendocrine reactivity to a novel environment (open field) and the adrenocorticotropic hormone (ACTH)/corticosterone response to a corticotropin-releasing factor (CRF) challenge were measured in 2-mo-old rats from four inbred strains derived from the Wistar-Kyoto rat: spontaneously hypertensive rats (SHRs), hypertensive and behaviorally hyperactive to novelty; WKY, neither hypertensive nor hyperactive; WKHA, hyperactive but normotensive; and WKHT, only hypertensive. The ACTH response to CRF was much lower in SHRs than WKYs, this reduced reactivity being clearly associated with the hyperactivity trait, since it was present in the WKHA and absent in the WKHT strain. On the other hand, the ACTH/corticosterone response to a psychological stimulus (open field) could not clearly discriminate the four strains. The largest difference was found in the prolactin response. Post-open-field levels were much lower in the WKHA (27.11 +/- 4.69 ng/ml) than in the parent WKY strain (83.65 +/- 6.84 ng/ml), the hypertensive strains having intermediate levels (WKHT: 58.05 +/- 7.65 ng/ml; SHR: 64.13 +/- 7.19 ng/ml). Other differences were also found in the levels of aldosterone and renin activity. These results indicate that these strains are an excellent model to study neuroendocrine correlates of hypertension and hyperactivity, which are associated in the SHR strain and may be of interest for the study of the association between neuroendocrine and behavioral characteristics.


2001 ◽  
Vol 119 (2) ◽  
pp. 54-58 ◽  
Author(s):  
José Carlos Peraçoli ◽  
Marilza Vieira Cunha Rudge ◽  
Maria Salete Sartori ◽  
Roberto Jorge da Silva Franco

CONTEXT: Animal models for essential hypertension have been used for understanding the human pathological conditions observed in pregnant hypertensive women. OBJECTIVE: To study the possible effects of pregnancy on hypertension and of hypertension on pregnancy in spontaneously hypertensive rats (SHR), and in their normotensive Wistar-Kyoto (WKY) counterparts. TYPE OF STUDY: Comparative study using laboratory animals. SETTING: Animal Research Laboratory of Clinical Medicine at the Medical School of Botucatu, São Paulo State University, Brazil. SAMPLE: Ten to twelve-week-old virgin female normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). The animals were separated into four groups: 15 pregnant spontaneously hypertensive rats (SHR-P), 10 non-pregnant spontaneously hypertensive rats (SHR-NP), 15 pregnant normotensive rats (WKY-P), and 10 non-pregnant normotensive rats (WKY-NP). MAIN MEASUREMENTS: The blood pressure was evaluated by the tail cuff method, in rats either with or without prior training for the handling necessary for tail cuff measurements. The maternal volemia expansion was indirectly evaluated by weight gain, and by systemic parameters as hematocrit, hemoglobin, total protein, albumin and sodium retention. The perinatal outcome of pregnancy was evaluated by analysis of resorptions, litter size, rate of low weight and number of stillbirths. RESULTS: The late fall in blood pressure in the pregnant SHR strain and in the normotensive WKY strain can only be detected in rats previously trained to accept the handling necessary for the tail cuff measurement. During pregnancy the body weight gain was significantly higher in WKY than in SHR rats. Systemic parameters were significantly lower in pregnant WKY rats than in non-pregnant WKY rats, while no differences were observed between pregnant and non-pregnant SHR groups. In pregnant WKY rats the sodium retention was higher from the 13th day onwards, while in SHR rats this occurred only on the 21st day. The characteristics of reproductive function such as number and weight of fetus, perinatal mortality and the resorption rate were significantly affected in the SHR strain. CONCLUSION: The SHR strain may be considered as a model for chronic hypovolemic maternal hypertension, with the fetal growth retardation being determined by this hypovolemic state.


1986 ◽  
Vol 250 (3) ◽  
pp. H443-H452 ◽  
Author(s):  
C. D. Sladek ◽  
M. L. Blair ◽  
Y. H. Chen ◽  
R. W. Rockhold

Abnormalities in the vasopressin (VP) and renin-angiotensin systems have been described in spontaneously hypertensive rats (SHR). Responsiveness of these systems to a decrease in plasma volume was examined in the SHR at 6, 8, and 18 wk of age and compared with responses in age-matched normotensive Wistar and Wistar Kyoto rats (WKY). Trunk blood was collected 3 h after administration of 2 ml/100 g body wt of 0.9% saline, 15 or 30% polyethylene glycol (PEG), and in one group of conscious 8- and 18-wk-old rats, mean arterial pressure was monitored following PEG administration. Hematocrit and serum VP increased significantly in both strains at all ages following PEG. At 6 and 8 wk of age, the VP response to the PEG injection was significantly greater in SHR compared with WKY (P less than 0.005), but at 18 wk the response was comparable in the two strains. Serum renin activity (SRA) also increased in both strains receiving PEG at 6 and 8 wk of age, but the response was suppressed in the SHR relative to the WKY (P less than 0.001). At 18 wk of age, SRA increased in WKY, but the response was totally suppressed in SHR. Renal renin content in a separate group of rats was reduced in 19-wk-old SHR compared with WKY (P less than 0.001) but was not different in 5- and 8-wk-old rats. Thus there appears to be a hyperresponsiveness in the VP system in young SHRs that is not present in the renin-angiotensin system. The divergence in the responsiveness of the renin and VP systems and the attenuation of responsiveness in the VP system in 18-wk SHRs indicate a differential effect of the hypertensive process on the VP and renin systems in the SHR.


2017 ◽  
Vol 313 (2) ◽  
pp. F450-F460 ◽  
Author(s):  
Regiane Cardoso Castelo-Branco ◽  
Deise C. A. Leite-Dellova ◽  
Fernanda Barrinha Fernandes ◽  
Gerhard Malnic ◽  
Margarida de Mello-Aires

The acute effects of angiotensin-1–7 [ANG-(1–7)] on the reabsorptive bicarbonate flow (J[Formula: see text]) were evaluated using stationary microperfusion in vivo in the proximal tubules of spontaneously hypertensive rats (SHR) and their normotensive controls, Wistar-Kyoto (WKY) rats, using a microelectrode sensitive to H+. In WKY rats, the control J[Formula: see text] was 2.40 ± 0.10 nmol·cm−2·s−1 ( n = 120); losartan (10−7 M) or A779 (10−6 M, a specific Mas antagonist), alone or in combination with losartan, decreased the J[Formula: see text]. ANG-(1–7) had biphasic effects on J[Formula: see text]: at 10−9 M, it inhibited, and at 10−6, it stimulated the flow. S3226 [10−6 M, a specific Na+-H+ exchanger 3 (NHE3) antagonist] decreased J[Formula: see text] and changed the stimulatory effect of ANG-(1–7) to an inhibitory one but did not alter the inhibitory action of ANG-(1–7). In SHR, the control J[Formula: see text] was 2.04 ± 0.13 nmol·cm−2·s−1 ( n = 56), and A779 and/or losartan reduced the flow. ANG-(1–7) at 10−9 M increased J[Formula: see text], and ANG-(1–7) at 10−6 M reduced it. The effects of A779, losartan, and S3226 on the J[Formula: see text] were similar to those found in WKY rats, which indicated that in SHR, the ANG-(1–7) action on the NHE3 was via Mas and ANG II type 1. The cytosolic calcium in the WKY or SHR rats was ~100 nM and was increased by ANG-(1–7) at 10−9 or 10−6 M. In hypertensive animals, a high plasma level of ANG-(1–7) inhibited NHE3 in the proximal tubule, which mitigated the hypertension caused by the high plasma level of ANG II.


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